Exploring pulmoprotection in COVID-19: Moving toward microRNA-based theranostics

The relentless struggle with the aftermath of COVID-19 has driven the medical community to seek innovative methods for predicting and managing the disease’s complications. Complications such as an overactive immune response, manifesting as cytokine storms, and shifts toward a procoagulant state not only exacerbate symptoms but also elevate the risk of mortality and long-term health issues. Consequently, there is a pressing need for novel diagnostic tools and therapeutic strategies that not only track disease progression and complications but also serve as potential drug targets or can be influenced by pharmacological interventions. In the presented study by Perez-Pons et al.1 titled “MicroRNA-centered theranostics for pulmoprotection in critical COVID-19,” the authors shed light on the promising role of microRNAs (miRNAs) as dual-purpose theranostic agents. By focusing on a multicenter cohort of intensive care unit (ICU) survivors, the research elucidates the potential of miRNAs in mitigating diffusion impairment—a common but debilitating consequence of severe infection. This commentary aims to contextualize these findings within the broader spectrum of molecular and cellular therapies, underlining their significance and implications they pose for the field. Since the outbreak of the COVID-19 pandemic, a significant number of survivors, particularly those who experienced severe illness, have continued to face post-acute pulmonary sequelae. COVID-19 survivors often experience a spectrum of long-term lung issues, with dyspnea being a common symptom reported by 42%–66% of individuals within 60–100 days post-infection.2 Individuals who experienced severe forms of COVID-19, particularly those in need of intensive respiratory support, are more likely to suffer from long-lasting lung issues.2 This includes diffusion impairment, which refers to a decreased ability of the lungs to transfer oxygen from the air into the bloodstream, as well as observable lung damage like pulmonary fibrosis on medical imaging.2 The persistence of these health issues among survivors indicates a substantial impact on their quality of life and the healthcare system, stressing the urgency in identifying effective interventions and support mechanisms for those affected

Methodological considerations for circulating long noncoding RNA quantification

In the past decade, significant resources have been invested in long noncoding RNA (lncRNA) research. Despite the knowledge available, we are far from incorporation of lncRNA into clinical practice. Here, we emphasize the technical challenges in the field, hoping to provoke a response leading to new consensus and guidelines

Long non‐coding RNA regulation of epigenetics in vascular cells

The vascular endothelium comprises the interface between the circulation and the vessel wall and, as such, is under the dynamic regulation of vascular signalling, nutrients, and hypoxia. Understanding the molecular drivers behind endothelial cell (EC) and vascular smooth muscle cell (VSMC) function and dysfunction remains a pivotal task for further clinical progress in tackling vascular disease. A newly emerging era in vascular biology with landmark deep sequencing approaches has provided us with the means to profile diverse layers of transcriptional regulation at a single cell, chromatin, and epigenetic level. This review describes the roles of major vascular long non-coding RNA (lncRNAs) in the epigenetic regulation of EC and VSMC function and discusses the recent progress in their discovery, detection, and functional characterisation. We summarise new findings regarding lncRNA-mediated epigenetic mechanisms—often regulated by hypoxia—within the vascular endothelium and smooth muscle to control vascular homeostasis in health and disease. Furthermore, we outline novel molecular techniques being used in the field to delineate the lncRNA subcellular localisation and interaction with proteins to unravel their biological roles in the epigenetic regulation of vascular genes

Uloga mikroRNK u regulaciji oksidativnog stresa

MicroRNAs (miRNAs) are small, 22-24 nucleotides long, noncoding RNAs that act as pivotal posttranscriptional regulators in various biological processes. Interaction of miRNAs with their target RNAs in most cases leads to the suppression of gene expression, by promoting degradation of RNAs or inhibiting translation. These interactions mainly occur with 3′ untranslated regions (UTR), but can also occur with 5′ UTR or with the coding part of the target RNA molecule. It is estimated that miRNAs regulate more than 30–60% of protein coding genes in the human genome. Oxidative stress refers to an imbalance between reactive oxygen species (ROS) generation and body's capability to detoxify the reactive mediators or to fix the relating damage. ROS can regulate miRNA transcription, maturation, and function. ROS directly modulate the activity of vital proteins that control posttranscriptional events in the biogenesis of miRNAs (Di George critical region-8 protein; Dicer). A certain group of transcription factors involved in the regulation of miRNA expression is upregulated under oxidative stress and directly activates the transcription of a subset of miRNAs. ROS have been directly implicated in epigenetic alternations such as DNA methylation and histone modifications that control specific microRNA transcription (1). On the other hand, miRNAs may in turn modulate the redox signalling pathways, altering their integrity, stability, and functionality, thus contributing to the pathogenesis of multiple diseases: cancer, neurodegenerative diseases, diabetes mellitus (2), ROS-related cardiac diseases, including myocardial infarction, ischemia/reperfusion injury, cardiac hypertrophy and heart failure, and are also considered as potential therapeutic targets and novel diagnostic tools.MikroRNK (miRNK) predstavljaju male, nekodirajuće RNK, dužine 22-24 nukleotida, koje regulišu ekspresiju gena na post-transkripcionom nivou. Interakcija miRNK sa ciljnim informacionim RNK (iRNK) u većini slučajeva dovodi do supresije ekspresije gena, degradacijom ciljne iRNK ili inhibicijom translacije. Ove interakcije se dešavaju na nekodirajućim 3’krajevima iRNK, ali mogu da se dese i na 5’ kraju ili čak na kodirajućem regionu ciljne iRNK. Smatra se da na ovaj način, u humanom genomu, miRNK kontrolišu oko 30-60% gena koji kodiraju proteine. Oksidativni stres je stanje u kome postoji neravnoteža između stvaranja reaktivnih vrsta kiseonika (slobodni radikali, ROS) i njihovog neutralisanja od strane antioksidativne zaštite organizma. Pokazano je da ROS mogu da utiču na procese transkripcije i sazrevanja miRNK kao i na njihovu funkciju. ROS direktno modulišu aktivnost glavnih proteina koji učestvuju u post-transkripcionoj obradi u procesu biogeneze miRNK (Di George critical region-8 protein i Dicer). Pod uticajem oksidativnog stresa može se aktivirati transkripcija određenih familija miRNK, dejstvom na transkripcione faktore koji učetvuju u tom procesu. Takođe, ROS utiču na epigenetske mehanizme regulacije ekspresije miRNK, kao što su DNK metilacija i modifikacija histona (1). Sa druge strane, miRNK mogu da utiču na aktivnost redoks signalnih puteva, menjajući njihovo funkcionisanje. Na taj način miRNK doprinose patogenezi mnogih bolesti kao što su: različite vrste kancera, neurodegenerativne bolesti, dijabetes melitus (2), bolesti srca, uključujući infarkt miokarda, povredu nastalu ishemijom/reperfuzijom, srčanu hipertrofiju i srčanu insuficijenciju. Takođe, miRNK se razmatraju kao potencijalni dijagnostički markeri i novi terapijski ciljevi.VIII Kongres farmaceuta Srbije sa međunarodnim učešćem, 12-15.10.2022. Beogra

Digital competence in laboratory medicine

Objectives: Even though most physicians and professionals in laboratory medicine have received basic training in statistics, experience shows that a general understanding of data analysis is not yet available on a broad scale. Therefore, data literacy, data-driven decision making, and computational thinking should be implemented in future educational training. To evaluate the state of digital competence among young scientists (YS) in laboratory medicine, we launched a worldwide online survey. Methods: A global online survey was conducted from 25/05/2022 to 26/06/2022 and was disseminated to YS who are listed in three large networks: YS of the DGKL, the EFLM Task Group-YS, and IFCC Task Force-YS and its corresponding members, covering a base of 53 countries. Results: A total of 119 young scientists from 40 countries participated in this survey. 80% did not learn digital skills in their academic education but 96% felt they needed to. Digital literacy was associated with terms such as programming, artificial intelligence and machine learning, statistics, communication, Big Data and data analytics. Conclusions: The results of our survey show that more knowledge and training in the area of digital skills is not just necessary, but also wanted by young scientists. A varied learning environment consisting of tutorial articles, videos, exercises, technical articles, collection of helpful links, online meetings and in person bootcamps is crucial to meet the challenges of an international project with different languages, health systems and time zones

LncRNAs as Regulators of Atherosclerotic Plaque Stability

Current clinical data show that, despite constant efforts to develop novel therapies and clinical approaches, atherosclerotic cardiovascular diseases (ASCVD) are still one of the leading causes of death worldwide. Advanced and unstable atherosclerotic plaques most often trigger acute coronary events that can lead to fatal outcomes. However, despite the fact that different plaque phenotypes may require different treatments, current approaches to prognosis, diagnosis, and classification of acute coronary syndrome do not consider the diversity of plaque phenotypes. Long non-coding RNAs (lncRNAs) represent an important class of molecules that are implicated in epigenetic control of numerous cellular processes. Here we review the latest knowledge about lncRNAs’ influence on plaque development and stability through regulation of immune response, lipid metabolism, extracellular matrix remodelling, endothelial cell function, and vascular smooth muscle function, with special emphasis on pro-atherogenic and anti-atherogenic lncRNA functions. In addition, we present current challenges in the research of lncRNAs’ role in atherosclerosis and translation of the findings from animal models to humans. Finally, we present the directions for future lncRNA-oriented research, which may ultimately result in patient-oriented therapeutic strategies for ASCVD

Multiomics tools for improved atherosclerotic cardiovascular disease management

Multiomics studies offer accurate preventive and therapeutic strategies for atherosclerotic cardiovascular disease (ASCVD) beyond traditional risk factors. By using artificial intelligence (AI) and machine learning (ML) approaches, it is possible to integrate multiple ‘omics and clinical data sets into tools that can be utilized for the development of personalized diagnostic and therapeutic approaches. However, currently multiple challenges in data quality, integration, and privacy still need to be addressed. In this opinion, we emphasize that joined efforts, exemplified by the AtheroNET COST Action, have a pivotal role in overcoming the challenges to advance multiomics approaches in ASCVD research, with the aim to foster more precise and effective patient care

Non-coding RNAs in preeclampsia—molecular mechanisms and diagnostic potential

Preeclampsia (PE) is a leading cause of maternal and neonatal morbidity and mortality worldwide. Defects in trophoblast invasion, differentiation of extravillous trophoblasts and spiral artery remodeling are key factors in PE development. Currently there are no predictive biomarkers clinically available for PE. Recent technological advancements empowered transcriptome exploration and led to the discovery of numerous non-coding RNA species of which microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are the most investigated. They are implicated in the regulation of numerous cellular functions, and as such are being extensively explored as potential biomarkers for various diseases. Altered expression of numerous lncRNAs and miRNAs in placenta has been related to pathophysiological processes that occur in preeclampsia. In the following text we offer summary of the latest knowledge of the molecular mechanism by which lnRNAs and miRNAs (focusing on the chromosome 19 miRNA cluster (C19MC)) contribute to pathophysiology of PE development and their potential utility as biomarkers of PE, with special focus on sample selection and techniques for the quantification of lncRNAs and miRNAs in maternal circulation

Integration of epigenetic regulatory mechanisms in heart failure

The number of “omics” approaches is continuously growing. Among others, epigenetics has appeared as an attractive area of investigation by the cardiovascular research community, notably considering its association with disease development. Complex diseases such as cardiovascular diseases have to be tackled using methods integrating different omics levels, so called “multi-omics” approaches. These approaches combine and co-analyze different levels of disease regulation. In this review, we present and discuss the role of epigenetic mechanisms in regulating gene expression and provide an integrated view of how these mechanisms are interlinked and regulate the development of cardiac disease, with a particular attention to heart failure. We focus on DNA, histone, and RNA modifications, and discuss the current methods and tools used for data integration and analysis. Enhancing the knowledge of these regulatory mechanisms may lead to novel therapeutic approaches and biomarkers for precision healthcare and improved clinical outcomes

Circulating resistin protein and mRNA concentrations and clinical severity of coronary artery disease

Introduction: Previous studies have implicated a strong link between circulating plasma resistin and coronary artery disease (CAD). The aim of this study was to evaluate the differences in peripheral blood mononuclear cells (PBMC) resistin mRNA and its plasma protein concentrations between the patients with CAD of different clinical severity. Material and methods: This study included 33 healthy subjects as the control group (CG) and 77 patients requiring coronary angiography. Of the latter 30 was CAD negative whereas 47 were CAD positive [18 with stable angina pectoris (SAP) and 29 with acute coronary syndrome (ACS)]. Circulating resistin was measured by ELISA; PBMC resistin mRNA was determined by real-time PCR. Results: Resistin protein was significantly higher in the ACS group compared to the CG (P = 0.001) and the CAD negative group (P = 0.018). Resistin mRNA expression did not vary across the study groups, despite the positive correlation seen with plasma resistin (rho = 0.305, P = 0.008). In patients, plasma resistin and PBMC resistin mRNA negatively correlated with HDL-C (rho = -0.404, P lt 0.001 and rho = -0.257, P = 0.032, respectively). Furthermore, the highest plasma resistin tertile showed the lowest HDL-C (P = 0.006). Plasma resistin was positively associated with serum creatinine (rho = 0.353, P = 0.002). Conclusion: Significant increase of plasma resistin in patients with ACS compared to CG and CAD negative patients was observed. Despite no change in PBMC resistin mRNA in different disease conditions a positive association between resistin mRNA and resistin plasma protein was evident. Both plasma resistin and PBMC resistin mRNA were negatively associated with plasma HDL-C, and plasma resistin positively with serum creatinine